This invention relates generally to suppository preparations and more specifically to a phased, systemic-delivery suppository preparation and its method of production.
As is well known, suppositories are medicated dosage forms inserted into body cavities such as the rectum, urethra, or vagina for the eventual delivery of one or more active agents to the systemic circulation and/or to local tissues. Suppositories are valuable, and often critical, additions to the symptom control armamentarium. This is especially true for those patients who, due to advanced disease, advanced age, nausea or other physiological or neurological problems, are unable to receive medications orally, intravenously or by injection. The problem is even more critical for the terminally ill patient who suffers from intense, intractable pain. Suppository dosage forms of medications presently being given to patients, particularly in the control of pain, are often times irregular in the delivery or bioavailability of the administered agents with the delivery of medications sometimes oscillating between levels which are far below the effective pain relieving dose to near toxic levels.
In recent years, prescribers have increasingly requested that pharmacists prepare extemporaneous suppository dosage forms for symptom control medications. However, because these dosage forms are not commonly compounded today, many prescribers who order drugs, the pharmacists who compound them, and the nurses who administer them, are unfamiliar with the criteria for properly formulated suppositories. Moreover, while suppository dosage forms have been formulated in the past for many agents, often the duration of the action of the drug is relatively short, requiring frequent administration thereby making usage inconvenient and/or ineffective. Attempts have been made, with limited success, to produce suppositories that are capable of delivering medications in a sustained or controlled release manner. Major obstacles include erratic absorption as herein described, and the timing of evacuations of the particular body cavity chosen for insertion. Many drugs can be delivered by the use of suppository dosage forms but the controlled release of such drugs has yet to be refined. Methods to prolong the action of drugs in a suppository sustained release form are therefore needed and desired.
Use of microparticles as a delivery system for drugs in clinical situations has been proven to be viable for many years. Since the advent of liposomes in the seventies, science has advanced to the point where many pharmaceutical materials are employed either singularly or in various percentages to produce optimum release rates for drugs or proposed drugs. However, prior art suppository preparations will typically release their active agents within the lower rectum thereby limiting the bioavailability of the agents. Substantial release of the active agent of the suppository into the lower rectum can and does limit the percentage of agent which can actually reach the systemic circulation system where it is needed.
It would be expedient, therefore, for the provision of a suppository formulation which will give more control over the release and bioavailability of medications. Furthermore, suppository preparations which are capable of releasing substantially all of their active agent(s) directly into the patient's systemic circulation instead of the lower rectum would greatly enhance the bioavailability and usefulness of such dosage forms and would substantially eliminate the problems associated with the untimely evacuation of the body cavity chosen for insertion.
The present inventor, through extensive experimentation and study, has developed a phased-release suppository delivery system incorporating a novel method of producing drug-ladened, polymeric "nanospheres" within a suppository base. The method of preparation of the "nanospheres" allows for the release of their active agent(s) only after a substantial number of the spheres have been transported across the capillary membranes of the rectum or other body cavity and have been taken up into the systemic circulation system. A small number of the spheres will inevitably become lodged within the mucus membrane of the chosen body cavity, however, even these spheres will, upon dissolution, release their active agent(s) from said area over an extended period of time.